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Cell-Cycle-Associated Expression Patterns Predict Gene Function in Mycobacteria.

Aditya C Bandekar1, Sishir Subedi2, Thomas R Ioerger2

  • 1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.

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|September 11, 2020
PubMed
Summary
This summary is machine-generated.

Mycobacterium tuberculosis (Mtb) exhibits cell-cycle-dependent gene regulation, with 485 oscillating genes linked to specific functions. This reveals a crucial coordination between primary metabolism and cell division in slow-growing bacteria.

Keywords:
Mycobacterium tuberculosiscell-cycle-associated transcriptioncytokinesisdivisome assembly and cytokinesisjust-in-time transcriptionnucleotide metabolismprokaryotic cell cycle

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Area of Science:

  • Microbiology
  • Molecular Biology
  • Cell Biology

Background:

  • Prokaryotic cell cycle progression is poorly understood, especially its coordination with transcriptional and metabolic changes.
  • Mycobacteria, with their temporally resolved DNA replication and cell division, offer a unique model for studying the prokaryotic cell cycle.

Purpose of the Study:

  • To investigate cell-cycle-dependent gene regulation in Mycobacterium tuberculosis (Mtb).
  • To identify genes with oscillating expression patterns correlating with the Mtb cell cycle.
  • To explore the coordination between primary metabolism and cell division.

Main Methods:

  • Characterization of temporal transcriptome changes in synchronously replicating Mtb populations.
  • Enrichment for genes exhibiting sinusoidal expression patterns.
  • Depletion studies of specific metabolic genes (pyrimidine synthesis, GuaB2) to assess phenotypic consequences.

Main Results:

  • Identified 485 periodically regulated genes (oscillating with cell cycle period) in Mtb.
  • Gene induction timing correlated with protein recruitment order during cytokinesis.
  • Pyrimidine synthesis gene expression peaked during DNA replication, while GuaB2 peaked during septation.
  • Depletion of pyrimidine synthesis genes caused filamentation; GuaB2 depletion perturbed septation.

Conclusions:

  • Demonstrated obligate coordination between primary metabolism and cell division in Mtb.
  • Identified specific genes and metabolic pathways critical for distinct cell cycle stages.
  • Highlighted the utility of Mtb as a model for prokaryotic cell cycle research.